NEURAL TUBE DEFECTS ( NTDs )

Department of Neurosurgery/Surgery and

Allied, Naseer Teaching Hospital

Dr. Sabiha Shah

Dr. Salman ur Rehman
 INTRODUCTION:

• Neural tube defects (NTDs) are:

• Birth defects of the central nervous system,
membranous ( meninges ) and bony ( skull
and vertebral column ) covers of CNS
• Originate during embryogenesis
• Result from failure of the morphogenetic
process of neural tube closure.
 EMBROYLOGY:
• In human embryos, notochord formation starts in 1st week
of gestation.
• In 2nd week of gestation, a plate of neuronal tissue, called
Neural plate is complete.
• Bending of the neural plate begins by 3rd week ( complete
approximately at 18 days ) after fertilization.
• An open cylindrical tube ( with both ends opened, anterior
neuropor & posterior neuropore ) is formed, called Neural
Tube.
• Anterior neuropore closure completes at approximately
25th day post fertilization
• Posterior neuropore closes completely by 28th day post
fertilization.
 NEUROLATION:
• Neural plate folding into neural tube
• At 3th week of gestation
• In the cranial region, neural tube folding and closure proceed
bidirectionally
• Spinal neurulation is entirely caudally directed as the embryo
continues to grow
• Primary neurulation completes with final closure of the
posterior neuropore on embryonic day 28.
• Impaired progression of closure and consequently the
presence of a persistently open posterior neuropore, results
in spinal and spinal cord NTDs.
• Impaired closure or persistently open anterior neuropore
results in cranial and brain NTDs.
• The type and size of the ensuing lesion relates directly to the
axial level at which closure stops.
• Embryologicaly, the neural tube is generated by
the processes that shape, bend and fuse the
neural plate, and fusion in the dorsal midline
progressively seals the neural tube as it forms. If
closure is not completed, the neuroepithelium
remains exposed to the environment and
consequently subject to degeneration and
neuronal deficit. The type and severity of these
open NTDs vary with the level of the body axis
affected. Thus failure of closure in the
prospective anterior neuropore ( brain ) and
posterior neuropore ( spinal cord ) results in
anencephaly/craniorachischisis and open spina
bifida ( cystica ) respectively.
• Simultaneously rolling up along the extent of
the rostrocaudal axis, neural tube closure is
discontinuous with distinct sites of initiation
located at characteristic axial levels. Moreover,
the morphological and molecular
requirements for closure vary along the body
axis, such that an individual NTD usually
affects only a portion of the neural tube. NTDs
can thus be attributed to failure of particular
initiation events or disruption of the
progression of closure between these sites.
 PATHOPHYSIOLOGY
• Studies of neurulation-stage embryos, both
normal and developing NTDs, provide insights
into key molecular and cellular pathways
underlying the morphological tissue
movements of neural tube closure. The
occurrence of isolated NTDs at cranial or
caudal levels in humans suggests the likely
involvement of region-specific mechanisms,
dependent on different gene products, in
addition to ubiquitous requirements that are
essential at all levels.
 Mechanism underlying Neural Tube
Closure
• Regulation of Cell Proliferation and Cell Death
• Shaping of the Neural Plate: Convergent
Extension Is Required to Initiate Closure
• PCP: planar cell polarity
• Bending of the Neural Folds: Regulation by
Shh and BMP Signaling
• Regulation of Cell Proliferation and Cell Death
EPIDEMIOLOGY
• Prevalence rate of NTDs is approximately 0.3
to 7.6 per 1000 live birth
• 30 % are syndromic, due to chromosomal or
genetic disturbance
• Approximately 70 % are due to nutritional
deficiency, specially vit B9 ( folic acid ) and
some times vit B12 ( mecobalamin )
• If 1st pregnancy is with NTD, chances of 2nd
offspring with NTDs is 2-3 times more than
previously normal 1st pregnancy.
 TYPES
A. Embryological (Lemire)
1. Neurolation Defects
a. Cranial
• Craniorachischisis
• Anencephaly
• Encephalocele
• Meningocele
b.Spinal
• Menigocele
• Myelomeningocele
• Myelocele

2. Post neurolation defects

a.Cranial
• Cranium bifida
• Microcephaly
• Hydranencephalay
• Holoprosencephlay
• Lissencephalay ( agyria, pachygyria &
polymicrogyria )
• Porencephalay
• Agenesis of corpus callosum
• Dandy walkers syndrome
• Absence of septum pallucidum
• Macroencephalay/ megalencephalay
• Heterotopias
• Schizencephalay
b. Spinal
• Split cord malformation ( diastematomyelia &
diplomyelia )
• Syringomyelia
• Hydromyelia
• Tethered cord syndrome
B. Morphological
1. Opened ( occulta ) NTDs
• Encephalocele
• Myelomeningocele
• Meningocele
• Lipomyelomeningocele

2. Closed ( cystica ) NTDs

• Spina bifida
• Cranium bifida
• Tethered cord syndrome
C. Anatomical
1. Cranial

• Cranium bifida
• Encephalocele
• Meningocele
2. Vertebral
• Spina bifida
• Meningocele
• Myelomeningocele
• Lipomyelomeningocele
• Tethered cord syndrome

3. Etiological
1. Syndromic (genetic/chromosomal)
2. Non Syndromic (nutritional)
 ETIOLOGY
• Many different possible causes, both genetic and
environmental
• Most NTDs are multifactorial, resulting from an
additive contribution of several risk factors, which
are each individually insufficient to disrupt neural
tube closure.
• The challenge of identifying the primary cause of
NTDs in individual patients is highlighted by the
numerous candidate genes and environmental
factors indicated by epidemiologic studies and
experimental models.
• Moreover, the potential for gene-gene and gene-
environment interactions introduces further
potential complexity.
 Risk Factors
• Any woman can have a baby with an NTD. But
there are factors that may make a woman more
likely than other women to have a baby with an
NTD. These are called risk factors.
• Nutritional deficiency, Vit B9 ( folic acid ) and Vit
B12 ( mecobalamin )
• A woman had a baby with an NTD, there is a 2-3
% more chance of having a baby with an NTD in
another pregnancy.
• Woman or her partner has a NTD or someone in
either of partners families has a NTD. This means,
have a family history of NTDs.
• Anti-seizure medicines, those having anti folate
activity.
• Obesity.
• Diabetes mellitus.
• Mother addiction, specially to opioids, in the
first 2 months of pregnancy.
• High body temperature early in
pregnancy. This may be caused by a fever or
by spending a lot of time in a hot tub or
sauna.
• Maternal infection, TORCH infection in
particular, in 1st trimester of pregnancy.
• Radiation exposure early in pregnancy.
• Mother’s age. Spina bifida is more common in
teen mothers.
• History of miscarriage. A woman who has had
miscarriages in the past has a higher risk of
having a baby with neural tube defects.
• Birth order. First-born babies are at higher
risk.
• Socioeconomic status. Children born into
lower socioeconomic families are at higher
risk for spina bifida. It is thought that poor
diet may be a factor.
 CLINICAL FEATURES
• Owing to the multifactorial causation, NTDs
represent a group of disorders.
• Clinically, presenting features depend on location
and type of NTDs.

CRANIAL:
In cranial NTDs, the open neural folds undergo
growth and differentiation and typically appear to
bulge from the developing brain, termed
exencephaly. Inability to form the skull vault over
the open region causes the exposed neural tissue
to degenerate, leading to the characteristic
appearance of anencephaly.
 Both anencephaly and craniorachischisis (~10%
of NTDs) are lethal conditions at or shortly
after birth
• Chraniorachischisis
• Anencephalay
• Skull mass, encephalocele/ meningocele
• Small skull ( microcephalay )
• Large brain ( macroencephalay ) with resultant
large head
• Seizure
• Neurological defecit
• Meningitis/ recurrent meningitis
• IQ problem/ mental retardation
SPINAL:
Open neural folds in the spinal region prevent
the sclerotome-derived vertebral arches from
covering the neuroepithelium, the consequent
opening in the vertebral column giving rise to
spina bifida. The neural tissues may be
contained within a meninges-covered sac that
protrudes through the open vertebrae
(myelomeningocele; spina bifida cystica) or
exposed directly to the amniotic fluid
(myelocele).
• Babies born with open spina bifida usually
survive with appropriate medical care but
suffer neurological impairment, the severity of
which depends on the level of the lesion.
Associated conditions include hydrocephalus,
Chiari malformation type II, and vertebral
abnormalities as well as genitourinary and
gastrointestinal disorders.
• Spinal lump
• Spinal Cutaneous symptoms/ signs
• Neurological defecit according to defect level
• Bowl bladder problem ( incontinence )
• Spinal deformity
• Chemical or pathogenic meningitis
• Neurogenic/ tropical ulcers in feet
• Back pain
• Etc……
 DIAGNOSIS
• Medical tests during pregnancy, called
screening tests to find out if baby is at
increased risk of having NTDs.
SCREENING TESTS:
• Maternal blood screening (quad screen): t’s
called a quad screen because it measures four
substances in mother blood (Alfa
Fetoprotein/AFP, human Chorionic
Gonadotropin/hCG, Inhibin A and Estriol). It is
done at 15 to 22 weeks of pregnancy.
• Ultrasound: Mother screening ultrasound at
16 to 20 weeks of pregnancy.

If screening tests show an increased risk of

NTDs, then diagnostic tests are recommended
to find out for sure if the baby has a NTD.

DIAGNOSTIC TESTS:
• Amniocentesis: An amniotic fluid taken from
uterus to check for birth defects, likely NTDs.
Taken at 15 to 20 weeks of pregnancy.
• High resolution probe ultrasound: Detailed
ultrasound of baby’s skull and spine, may
require vaginal ultrasound.
• MRI: A detailed MRI of fetus for NTDs.
 MANAGEMENT

It Is Better To Prevent Than Cure,

is an old adage
But
IT IS FAR BETTER TO PREVENT
NTDs THAN TREAT
 Prevention
• To help prevent NTDs, give every fertile
married woman a vitamin supplement that
has 400 micrograms of folic acid in it every
day, even if she is not trying to get pregnant.
• Folic acid helps prevent NTDs only if it is taken
Before conception and in the first 4 to 6
weeks of pregnancy.
• A woman at high risk for NTDs, should take
4,000 micrograms of folic acid every day.
• Taking folic acid before and during early
pregnancy can help prevent NTDs. NTDs
happen in the first month of pregnancy,
before even a woman may know she is
pregnant. This is why it’s important to have
enough folic acid in body before pregnancy.
 Can you get folic acid from food..??
Yes! you can get folic acid from foods that are fortified
with folic acid. Fortified means a food has folic acid
added to it. Check the product label to see how much
folic acid you get in each serving. Look for the word
“fortified” or “enriched” on labels on foods like:
• Bread
• Breakfast cereal
• Cornmeal
• Flour
• Pasta
• Products made from a kind of flour called corn masa,
like tortillas, tortilla chips, taco shells, tamales and
pupusas
• White rice
 Some fruits and vegetables are good sources of
folic acid. When folic acid is naturally in a food, it’s
called folate. Foods that are good sources of folate
are:
• Beans, like lentils, pinto beans and black beans
• Leafy green vegetables, like spinach and Romaine
lettuce
• Asparagus
• Broccoli
• Peanuts
• Citrus fruits, like oranges and grapefruit
• Orange juice
• It’s hard to get all the needed folic acid from food.
Even if foods that are rich in folic acid, are taken,
give every pregnant woman in early weeks or those
who want to become pregnant, vitamin supplement
containing atleast 400 mcg folic acid each day, too.

• If baby has an ONTD, a cesarean section is better to

deliver baby. This is often done to lower the risk for
damage to the spinal cord and brain that may occur
during a vaginal delivery.
 TREATMENT
• To Fix and close the neural tube defect
• To Treat hydrocephalus
• To Treat bone (orthopedic) problems
• To Repair bowel and bladder problems
• To Treat other concomitant congenital
anamolies
Rehabilitation:
• Positioning aids that help the child sit, lie, or
stand
• Braces and splints that help prevent deformity
and give support or protection to areas of the
body
• Medicines
 MANAGEMENT PILLARS
1. NUTRITIONIST & GENETICS EXPERT
2. GYNAECOLOGIST AND OBSTETRICIAN
3. NEONATOLGIST & PEDIATICIAN
4. NEUROSURGEON
5. OTHERS ;
• PEDIATRICS SURGEON
• UROLOGIST
• PLASTIC SURGEON
• ORTHOPEDICS SURGEON
• REHIBILITATOR
THANK YOU.